目的观察蝎毒耐热蛋白(SVHRP)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)致帕金森病小鼠运动协调性和脑内神经元型一氧化氮合酶(nNOS)免疫反应(IR)阳性神经元的影响。方法C57BL/6小鼠颈部scMPTP20mg/kg,连续8d造模型。同时设立SVHRP治疗组,测定小鼠爬竿和游泳时间以检测其运动协调性。应用免疫细胞化学方法观察脑内黑质酪氨酸羟化酶(TH)和nNOS免疫反应阳性神经元的变化。结果MPTP致模型小鼠在黑质致密部多巴胺能神经元损伤后,运动协调能力下降,同时在尾核的nNOS免疫反应阳性神经元细胞数较正常组增多。治疗组小鼠运动协调能力与正常对照组比较没有明显改变,尾核的nNOS免疫反应阳性神经元细胞数较模型组明显减少。结论SVHRP可以保护中脑黑质致密部多巴胺能神经元及改善MPTP引起的运动协调性降低,逆转MPTP引起的尾核nNOS免疫反应活性增强。而NO可能参与其保护机制。

Objective To observe the effects of scorpion venom heat-resistant protein (SVHRP) on the locomotor ability and immunoreactivity (IR) of neural nitric oxide synthase (nNOS) in C57BL/6 mice with Parkinson's disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Methods C57BL/6 Mice were sc injected with MPTP (20 mg/kg) for 8 d, then the pole test and swimming test were conducted to testify their motor harmony in SVHRP group. Immunocytochemistry was used to observe the change of TH-IR positive neurons in substantia nigra and nNOS-IR positive neurons in caudatum, respectively. Results The results indicated that MPTP model mice showed locomotor deficits after the damage of dopaminergic neurons. Meanwhile, the number of nNOS-IR positive neurons in caudatum increased as compared to the normal group. Furthermore, the therapy group had no difference in locomotor harmony compared with the normal control group, but the number of nNOS-IR positive neurons in caudatum decreased significantly as compared to the model group. Conclusion This study suggests that the increase of nNOS in caudatum may play a role in improvement of locomotor disability. SVHRP exerts neuroprotection in MPTP-treated C57BL/6 mice via decreasing nNOS in the caudatum. NO may be related to the protective mechanism.

国家自然科学基金资助项目(60472017)